We have discovered that the the fast repetitive presentation of a visual checkerboard (a photic """"""""tetanus"""""""") leads to a persistent enhancement of early components of the visual evoked potential in normal humans. This lasting enhancement of the visual evoked potential is thought to be a form of human long-term potentiation (LTP) - the neuronal process underlying learning and memory. The potentiated response is largest in the hemisphere contralateral to the tetanized visual hemifield, and is limited to one component of the visual evoked response. Exposure to a photic tetanus also results in improved performance in a behavioral task. This study will be the first to investigate non-invasively the parameters and possible mechanisms of a form of LTP in humans. The goal of this proposal is to: 1) determine the optimal stimulus parameters of this potentiation, and 2) determine if this potentiated response obeys the established rules and cellular mechanisms of LTP and long-term depression (LTD) and 3) study its behavioral relevance. The study involves three research sites. The overall design, coordination, and animal studies will be by Dr. Teyler, at the University of Idaho, the co-discoverer of """"""""human LTP"""""""". The optimal stimulus parameters and """"""""rules testing"""""""" will be by Drs. Kirk and Hamm at the University of Auckland, New Zealand. The Yale site, led by Drs. Cavus and Krystal, will test whether the potentiation of this visual evoked response in humans is dependent on NMDA receptor activity. This study will provide us for the first time with tools to assess cortical plasticity noninvasively in humans. Such ability could have future applications in better understanding LTP and in the assessment of disorders that are thought to involve impairment in the cortical plasticity, such as Alzheimer's disease, Depression and Schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH064508-02
Application #
6860150
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Anderson, Kathleen C
Project Start
2004-03-01
Project End
2007-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
2
Fiscal Year
2005
Total Cost
$250,853
Indirect Cost
Name
University of Idaho
Department
Administration
Type
Schools of Education
DUNS #
075746271
City
Moscow
State
ID
Country
United States
Zip Code
83844
Clapp, Wesley C; Hamm, Jeff P; Kirk, Ian J et al. (2012) Translating long-term potentiation from animals to humans: a novel method for noninvasive assessment of cortical plasticity. Biol Psychiatry 71:496-502
Ross, Robert M; McNair, Nicolas A; Fairhall, Scott L et al. (2008) Induction of orientation-specific LTP-like changes in human visual evoked potentials by rapid sensory stimulation. Brain Res Bull 76:97-101
Zaehle, Tino; Clapp, Wesley C; Hamm, Jeff P et al. (2007) Induction of LTP-like changes in human auditory cortex by rapid auditory stimulation: an FMRI study. Restor Neurol Neurosci 25:251-9
Clapp, Wesley C; Eckert, Michael J; Teyler, Tim J et al. (2006) Rapid visual stimulation induces N-methyl-D-aspartate receptor-dependent sensory long-term potentiation in the rat cortex. Neuroreport 17:511-5
McNair, Nicolas A; Clapp, Wes C; Hamm, Jeff P et al. (2006) Spatial frequency-specific potentiation of human visual-evoked potentials. Neuroreport 17:739-41
Clapp, Wesley C; Muthukumaraswamy, Suresh D; Hamm, Jeff P et al. (2006) Long-term enhanced desynchronization of the alpha rhythm following tetanic stimulation of human visual cortex. Neurosci Lett 398:220-3
Clapp, Wesley C; Zaehle, Tino; Lutz, Kai et al. (2005) Effects of long-term potentiation in the human visual cortex: a functional magnetic resonance imaging study. Neuroreport 16:1977-80
Clapp, W C; Kirk, I J; Hamm, J P et al. (2005) Induction of LTP in the human auditory cortex by sensory stimulation. Eur J Neurosci 22:1135-40
Teyler, Timothy J; Hamm, Jeff P; Clapp, Wesley C et al. (2005) Long-term potentiation of human visual evoked responses. Eur J Neurosci 21:2045-50